Cancer is a class of diseases which occur because cells become immortalised; they fail to heed customary signals to turn off growth which is a normal function of remodelling in the body that requires cells to die on cue. Apoptosis, or programmed cell death, can become defective and when this happens malignant transformation can take place. The immortalised cells grow beyond their normal limits and invade adjacent tissues. The malignant cells may also metastasise and spread to other locations in the body via the bloodstream or lymphatic system. Cancer cells often form a mass known as a tumour.
There are about 200 different types of cancer; the cancers can start in any type of body tissue although many cancers will metastasise into other body tissues. There are many different causes of cancer and these include; carcinogens, age, genetic mutations, immune system problems, diet, weight, lifestyle, environmental factors such as pollutants, some viruses, for example, the human papilloma virus (HPV) is implicated in cervical cancer.
There are many different treatment options for cancer and the treatment sought is often determined by the type and stage of the cancer. Treatment options include; chemotherapeutic drug treatment, hormonal drug treatment, radiotherapy, surgery, complementary therapies and combinations thereof.
Cannabis has been ascribed to be both a carcinogen and anti-cancer agent. In particular smoking cannabis is known to be carcinogenic as the cannabis smoke contains at least 50 different known carcinogenic compounds, many of which are the same substances found in smoked tobacco. One of these carcinogens, benzopyrene is known to cause cancer as it alters a gene called p53, which is a tumour suppressor gene.
Researchers have discovered that some cannabinoids, including tetrahydrocannabinol (THC) and cannabidiol (CBD) are able to promote the re-emergence of apoptosis so that some tumours will heed the signals, stop dividing, and die. The process of apoptosis is judged by observation of several phenomena including: reduced cellular volume, condensation of nuclear chromatin, changes in distribution of phospholipids in plasma membrane phospholipids, and cleavage of chromatin into DNA fragments called DNA ladders.
Another method by which tumours grow is by ensuring that they are nourished: they send out signals to promote angiogenesis, the growth of new blood vessels. Cannabinoids may turn off these signals as well.
Cannabinoids have been shown to have an anti-proliferative effect on different cancer cell lines. The cannabinoids THC, tetrahydrocannabinol acid (THCA), CBD, cannabidiolic acid (CBDA), cannabigerol (CBG) and cannabichromene (CBC) and the cannabinoid extracts enriched in either THC or CBD were tested on eight different cell lines in Ligresti et al., (2006). The lines used in this study were: DU-145 (hormone-insensitive prostate cancer), MDA-MB-231 and MCF-7 (breast cancer), CaCo-2 (colorectal cancer), LiMol (thyroid cancer), RBL-2H3 (leukaemia), AGS (gastric cancer) and C6 (glioma cells).
The data for each cannabinoid in each different type of cancer varied but generally the best data were observed with CBD or the cannabis extract enriched in CBD.
The IC50 values varied widely between the different cannabinoids and the different cell lines; however the authors determined that the cannabinoid CBD was the most effective in the breast cancer cell lines.
Several patent applications describe the use of cannabinoids in the treatment of brain tumours, for example WO 2009/147439 describes a combination of THC and CBD in the treatment of glioma, WO 2009/147438 describes the use of THC and CBD in combination with non-cannabinoid chemotherapeutic agents in the treatment of glioma and WO 2011/110866 describes the use of THC and CBD with temozolamide in the treatment of glioma.
The patent EP1,802,274 describes the use of the cannabinoid CBD in the inhibition of tumour cell migration.
A later study ascribed a mechanism to this, by demonstrating that CBD is able to able to down-regulate the expression of the DNA binding protein inhibitor, Id-1 in human breast cancer cells (McAllister, 2007). The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion.
CBD has also been shown to inhibit human cancer cell proliferation and invasion through differential modulation of the ERK and ROS pathways, and that sustained activation of the ERK pathway leads to down-regulation of Id-1 expression. It was also demonstrated that CBD up-regulates the pro-differentiation agent, Id-2. Using a mouse 4T1 cell line and a model of metastatic breast cancer, CBD significantly reduced metastatic spread. As such CBD may represent a promising treatment of breast cancer in patients with secondary tumours (McAllister, 2007).
The patent application GB2494461 describes the use of the cannabinoids CBG, CBDV and THCV in the treatment of U87 glioma cells.
Choi et al. (2008) describes the efficacy of CBD in a number of cell lines and that the cytotoxicity of CBD increased in a dose and time dependant manner. Furthermore Baek et al. (1996) suggests that CBG exerts an anti-tumour activity against melanoma cells in a mouse model.
It is an object of the present invention to find improved and/or alternative cancer therapies. To this end a platform of data representing the use of an API comprising or consisting essentially of a combination of cannabidiol with another cannabinoid selected from cannabigerol (CBG), cannabigerolic acid (CBGA), cannabidiolic acid (CBDA), and tetrahydrocannabivarin (THCV) in various cancer cell lines.